GB2101601A - Bisphosphine synthesis - Google Patents

Abstract

A process for the synthesis of a bisphosphine comprises: (i) preparation of a bisphosphonium salt, (ii) hydrolysis of the bisphosphonium salt to yield a bisphosphine oxide and (iii) reduction of the bisphosphine oxide to yield a bisphosphine. Some of the bisphosphines so produced are stated to be novel as are intermediate bisphosphonium salts, bisphosphine oxides and mixed phosphine-phosphine oxides, phosphonium salt-phosphine oxides and phosphine-phosphonium salts. The bisphosphines are suitable inter alia as liquids.

Description

SPECIFICATION Synthesis of unsymmetrical phosphines This invention relates to the synthesis of organophosphorus compounds and in particular provides a novel process for the synthesis of bisphosphines suitable inter alia as ligands, and further provides novel intermediate bisphosphonium salts, bisphosphine oxides, and mixed phosphine-phosphine oxides, phosphonium salt-phosphine oxides and phosphine-phosphonium salts.In our copending British Patent Application No. 8116341 filed concurrently herewith, we disclose a catalytic process for saturating or partially saturating and/or extending the carbon chain length of an unsaturated organic compound comprising contacting said compound with hydrogen and/or carbon monoxide in the presence as catalyst of a complex or compound of a platinum group metal, and an unsymmetrical bisphosphine of general formula A(CH2)nB in which A and B are different phosphine moieties, A having the formula R2P and B having the formula either R'2P or RR'P where R represents an aryl group and R' represents an aralkyl, alkaryl or alkyl group and n is an integer between 1 and 10 inclusive, or an unsymmetrical monophosphine of formula R2R'P where R and R' are as defined above.

Symmetrical bisphosphines are known in the art and certain unsymmetrical bisphosphines having the general formula RPhP(CH2)nPPh2 where R is alkyl and n is 1,2 or 3 are also known per se, having been synthesised by a process described in= J Am. Chem. Soc., 1974, 96, p. 341 6 and in J Organomet Chem., 1975, 94, p. 327. However, the starting materials are not readily available and the reactions are lengthy and require careful control of conditions.

It is the object of the present invention to provide a novel process for the synthesis of bisphosphines and which does not suffer from the disadvantage of the prior art process.

According to a first aspect of the invention, therefore, a process for the synthesis of a bisphosphine comprises (i) preparation of a bisphosphonium salt, (ii) hydrolysis of the bisphosphonium salt to a bisphosphine oxide and (iii) reduction af the bisphosphine oxide to yield a bisphosphine.

Preferably the salt is a divalent salt and the oxide is a dioxide.

According to further aspects of the invention, we provide novel compositions of matter comprising certain bisphosphines, bisphonium salts, bisphosphine oxides and mixed phosphinephosphine oxides, mixed phosphonium salt-phosphine oxides and mixed phosphine-phosphonium salts.

Bisphosphines produced according to the first aspect of the. invention have the general formula A(CH2)nB where A and B are the same or different phosphine moieties and have the formula R2P, R'2P or RR'P where R and R' represent an aryl, aralkyl, alkaryl, or alkyl group, and n is an integer greater than or equal to 1. The R or R' groups may be substituted for example by an alkoxy group such as methoxy. The process may be applied to the synthesis of phosphines having any length of carbon chain, but we are particylarly concerned with values of n from 1 to 10, preferably from 3 to 6, inclusive.

Unsymmetrical bisphosphines where n > 4 are novel compounds.

Bisphosphonium salts according to further aspects of the invention have the general formula [A'(CH2)nB12+X2- where A' and B' are the same or different phosphonium moieties having the formula R3P, R2R'P, R' 3P or RR'2P where R, R' and n are as defined above, and X represents a divalent anion or two monovalent anions which may be the same or different, for example halides. Bisphosphine oxides according to further aspects of the invention have the general formula A" (O)(CH2)n(O)B" where A" and B" are the same or different phosphine moieties having the formula R P RR'P or R' 2P where R, R' and n are as defined above.By an "aralkyl" group in the above, we mean aryl-substituted alkyl groups such as benzyl Ph-Ch2-, and by "alkaryl" we mean alkyl-substituted aryl such as p-tolyl p-CH 3C6H4.

In the first stage of the process according to the first aspect of the invention, the bisphosphonium salt may be prepared either (i) by reaction of a bis(diarylphosphino)alkane with, successively, two organic halides, which may be the same or different, being either alkyl and/or aryl halides, or (ii) by reaction of dihaloalkane with, successively, two tertiary monophosphines, which may be the same or different, being either aryl phosphines and/or aryl alkyl phosphines.

Embodiments of reaction (i) of the above alternatives may conveniently be represented by

in which, R R' and X and n are defined as above.

Embodiments of reaction (ii) of the above alternatives may conveniently be represented by

In some cases it is necessary that the first stage reaction stops at the monophosphonium salt stage to prevent formation of any symmetrical biphosphonium salt. Factors which we have found to influence this aspect of the reactions include the polarity of the solvent, the relative solubilities in the solvent of the mono and bis salts and the temperature and duration of the reaction. We have found that reaction scheme (ii) is in general to be preferred, since it is easier to stop at the first stage. A method which is generally successful is to react a dibromoalkane with a first mono-tertiary phosphine in a nonpolar solvent and then with a second mono-tertiary phosphine in a polar solvent.Examples of suitable non-polar solvents are benzene and toluene and examples of suitable polar solvents are sulpholane, dimethylformamide, nitromethane and nitrobenzene. For values of n > 5, it is preferred to use an excess of the reactant dibromoalkane as non-polar solvent to prevent formation of the symmetrical bisphosphonium salt. For very low values of n, particularly n =2, the second stage yield is reduced, presumably due to the greater proximity of the two positively charged phosphorus atoms.

Table 1 gives details of various phosphonium salts produced according to the first stage of the process of the invention. They were found generally to be more readily soluble in organic solvents such as ethanol and chloroform than the analogous symmetrical compounds. Compounds numbers 20-23 formed initially as oils which, when cool, formed a hard transparent "glass" on the walls of the reaction vessel. All compounds were characterised by their 1H n m r spectra.

In Table 1, a could not be crystallised; character by 'H n m r. Although elemental analyses could not be obtained, compounds (10), (1 1), (14), (15) and (17) were used without purification to produce analytically pure phosphine oxides. b, Poor analysis probably due to contamination with unreacted monophosphonium salt. c, Identical results are obtained with DMF as solvent. Abbreviation: DMF = dimethylformamide.

In the second stage of the process according to the first aspect of the invention, the bisphosphonium salt is hydrolysed to a bisphosphine oxide preferably by alkaline hydrolysis with boiling aqueous sodium or potassium hydroxide.

We have found that, as expected from theoretical considerations, the R group preferentially ejected on hydrolysis from each end of the bisphonium salt molecule is generally that which forms the most stable anion, the ease of displacement thus being benzyl > phenyl > methyl > 2-phenylethyl > ethyl > higher alkyls.

Surprisingly, the presence of a benzyl group at one end of a salt molecule appears to upset the above order at the other end so that, for example, a methyl group is ejected in preference to phenyl.

Bisphosphine oxides are thus difficult to prepare in good yield from bisphosphonium salts containing a benzyl group, but such salts are nevertheless useful as intermediates in the preparation of certain novel mixed compounds according to the second aspect of the invention.

TABLE 1 PREPARATIVE DETAILS FOR PHOSPHONIUM SALTS

Reaction Yield M.p.(1 lt) Phosphonium Salt Made from:- Solvent time (%) ( C) Analysis (th.) 1. [Ph2P(CH2)6PPh2.CH2Ph]Br Ph2P(CH2)6PPh2 + PhCH2Br Toluene 1 hr 83 275-8 C 70.6 (71.0), H 6.2 (6.3) 2. [PhCH2.Ph2P(CH2)6PPh.CH2Ph]Br2 Ph2P(CH2)6PPh2 + 2PhCH2Br Toluene 4 hr 98 286-9 C 66.6 (66.3), H 5.7 (5.8) 3. [MePh2P(CH2)6PPh2.CH2Ph]Br I (1) + Me I CH2Cl2 20 min 100 216-20 C 59.5 (59.5) H 5.5 (5.5) 4. [EtPh2P(CH2)6PPh2.CH2Ph]Br I (1) + Et I CH2Cl2 20 min 100 220-4 C59.5(59.9), H 5.6 (5.7) 5. [EtPh2(CH2)6PPh2Et]I2 Ph2P(CH2)6PPh2 + 2 Et I CH2Cl2 20 min 90 258-61 C 53.0 (52.3), H 5.5 (5.5) 6. [Br(CH2)6PPh3]Br Br(CH2)6Br + Ph3P Br(CH2)6Br .1 hr 88 130-2 C 57.6(56.9), H 5.4 (5.4) (100 C) 7. [Ph3P(CH2)6PPh3]Br2 Br(CH2)6Br + 2 Ph3P Toluene 1 hr 78 298-304 (335) (Known compound) 8. [MePh2P(CH2)6PPh3]Br2 (6) + MePh2P DMF 2 hr 90 213-8 C 61.0 (62.9), H 5.9 (5.7) 9. [EtPh2P(CH2)6PPh3]Br2 (6) + EtPh2P DMF 4 hr 82 218-23 C 61.2 (63.3), H 5.9 (5.9) 10. [-cC6H11.Ph2P(CH2)6PPh3]Br2 (6) +cC6H11Ph2P DMF 4 hr 80 Oilya 11. [(p-CH3C6H4)3P(CH2)6PPh3]Br2 (6) + (p-CH3C6H4)3P DMF 2 hr 85 Oilya 12. [Br(CH2)4PPh3]Br Br(CH2)4Br + Ph3P Toluene 8 hr 88 206-7 (205) (Known compound) 13. [Ph3P(CH2)4PPh3]Br2 (12) + Ph3P DMF 3 hr 81 264-8 (290) (Known compound) 14. [MePh2P(CH2)4PPh3]Br2 (12) + MePh2P DMF 4 hr 97 Oilya 15. [EtPh2(CH2)4PPh3]Br2 (12) + EtPh2P DMF 5 hr 88 Oilyh 16. [Br(CH2)3PPh3]Br Br(CH2)Br + Ph3P Toluene 5 hr 84 221-2 (210-5) (Known compound) 17. [EtPh2P(CH2)3PPh3]Br2 (16) + EtPh2P DMF 5 hr - Oilya TABLE 1 (Continued) PREPARATIVE DETAILS FOR PHOSPHONIUM SALTS

Reaction Yield M.p. (1 lt) Phosphonium Salt Made From:- Solvent time (%) ( C) Analysis (th.) 18. [Br(CH2)2PPh3]Br Br(CH2)2Br + Ph3P Toluene 5 hr 76 303-6 (208) (Known Compound) 19. [MePh2P(CH2)2PPh3]Br2 (18) + MePh2P DMF 20 hr 48 278-84 C 56.5 (60.9), H 5.2 (5.0) b 20. [Ph2P(CH2)2PPh2Me]I Ph2P(CH2PPh2 + Me I Toluene 2 hr 70 "Glass"a 21. [Ph2P(CH2)2PPh2Et]I Ph2P(CH2)2PPh2 + Et I Toluene 3 hr 75 "Glass"a 22. [Ph2P(CH2)2PPh2Pr]I Ph2P(CH2)2PPh2 + 1Pr I Toluene 4 hr 72 "Glass"a 23. [Ph2PCH2PPh2Et]I Ph2PCH2PPh2 + Et I Toluene 3 hr 68 "Glass"a In order satisfactorily to effect the second stage of the process of the invention, therefore, it is preferred to carry out the hydolysis on bisphosphonium salts which do not contain a benzyl group.

Bisphosphine oxides are readily formed from bisphosphonium salts which contain aryl or alkaryl groups, the following schemes illustrating embodiments of this stage of the process:

in which R represents alkyl and Ar represents aryl (other than phenyl) and alkaryl, and n is greater than 2. The products were obtained initially as hygroscopic viscous oils which were crystallised from sodium-dried toluene and diethyl ether as white powders which were dried under vacuum. Table 2 gives details of various phosphine oxides prepared according to the second stage of the process of the invention; all were characterised by their XH n m r spectra, and some were additionally characterised by their 31P n m r spectra.

TABLE 2 Bisphosphine Oxides prepared by Hydrolysis of Bisphosphonium Salts with Aqueous Sodium Hydroxide

Yield M.p.(lit) Phosphine Oxide Precursor (%) ( C) Analysis (th.) (1) Ph2P(O)(CH2)6P(O)Ph2 Ph3P(CH2)6PPh2Br2 100 195(196) (Known compound) " (PhCh2)Ph2P(CH2)6PPh2(CH2Ph)Br2 100 194(196) " (2) Ph2P(CH2)6P(O)Ph2 Ph2P(CH2)6PPh2(CH2Ph)Br 94 169-79 C 74.6(76.5), H 6.8(6.9) (3) (p-CH3C6H4)3P(O)(CH2)6P(O)Ph2 (p-CH3C6H4)3P(CH2)6PPh3Br2 63 150-60 C 74.8(74.7), H 7.2(7.1) (4) MePhP(O)(CH2)6P(O)Ph2 MePh2(CH2)6PPh3Br2 90 62-70 C 70.8(70.7), H 7.0(7.1) (5) EtPhP(O)(CH2)6P(O)Ph2 EtPh2P(CH2)6PPh3Br2 74 88-94 C 70.3(71.2), H 7.2(7.4) (6) c-C6H11PhP(O)(CH2)6P(O)Ph2 c-C6H11Ph2P(CH2)6PPh3Br2 38 163-65 C 70.5(73.2), H 7.3(7.8) (7) MePhP(O)(CH2)4P(O)Ph2 MePh2P(CH2)4PPh3Br2 94 Oil C 64.5(69.7), H 6.4(6.6)a (80 EtPhP(O)(CH2)4P(O)Ph2 EtPh2P(CH2)4PPh3Br2 75 142-50 C 69.1(70.2), H 6.6(6.9) (9) EtPhP(O)(CH2)3P(O)Ph2 EtPh2P(CH2)4PPh3Br2 53 141-42 C 69.5(69.7), H 6.5(6.6) (10) p-tol2P(O)(CH2)6P(O)Ph2 p-tol3P(CH2)6PPh3Br2 54 150-54 C74.8(74.1), H 7.2(7.1) aThe poor +analytical data are ascribed to the oily and intractable nature of this very hygroscopic substance.

Compounds number 4 to 9 in Table 2 each contain a chiral centre at one of the phosphorus atoms In the third stage ot the process according to tiie first aspect of the invention, the bispnosphine oxide is reduced using a reducing agent which preferably retains or inverts the configuration of the substituent groups at the phosphorus atoms. Suitable reducing agents are the chlorosilanes, the most satisfactory being trichlorosiiane which retains or, in the presence of an amine such as triethylamine, inverts the configuration of the phosphorus atoms.

An embodiment of this stage of the process is represented by the following reaction:

Table 3 gives details of various unsymmetrical chiral and achiral bisphosphines produced according to this process. Most are relatively air-stable, low melting crystalline solids, except for the methyl derivatives which are waxes and are more susceptible to oxidation in air. All are much more soluble in ethanol and other similar solvents than corresponding symmetrical bisphosphines. All except the ethyl derivative where n = 3 are new compositons of matter.

TABLE 3 Unsymmetrical Bisphosphines

RRP(CH2)nPPh2 R R n P configuration Yield, (%) M.p., ( C) Analysis (th.), (%) 1 Me Ph 6 chiral 93 Waxy C 76.7(76.5), H 7.9(7.7) 2 Et Ph 6 chiral 64 44-46 C 76.2(76.8), H 7.8(7.9), P 14.7(15.2) 3 c-hex Ph 6 chiral 57 84-93 C 77.9(78.2), H 7.9(8.3), P 13.2(13.5) 4 Me Ph 4 chiral 70 Waxy C 74.4(75.8), H 7.4(7.2) 5 Et Ph 4 chiral 58 49-50 C 76.0(76.2), H 7.3(7.5), P 16.0(16.4) 6 Et Ph 3 chiral 62 60-69 C 75.5(75.8), H 7.2(7.2), P 16.8(17.0) 7 p-tol p-tol 6 achiral 20 62-4 The process of the invention is now described with reference to the following preparative examples, of which Example 1 descnbes the preparation of starting material and Example2 illustrates embodiment of the invention.

General Methyldiphenylphosphine, ethyldiphenylphosphine, bis(disphenylphosphino)-methane and 1 ,2bis(disphenylphosphino)ethane were prepared by literature method. Tetrahydrofuran:and Analar toluene were dried over sodium wire.

1H n.m.r. spectra were recorded for solutions in deuterochloroform ord6-dimethylsulphoxide on a Perkin-Elmer R12 spectrometer.

EXAMPLE 1 1 ,6-Bis(di phenylphosphino)hexane, (dph): A solution of lithium diphenylphosphide was prepared by stirring triphenylphosphine (1 31.0 g, 0.5 mol) and then strips of lithium metal (7.0 g, 1.0 g atom) in dry THF (400 cm3) under nitrogen for 3 hr.

Phenyl lithium was destroyed by the dropwise addition of tertiarybutyl chloride (46.0 g, 0.5 mol), allowing the solution to reflux during the exothermic reaction. 1 ,6-Dichlorohexane (38.0 g, 025 mol) in dry THF (200 cm3) was then added dropwise, keeping the temperature less than 1 OOC. The mixture was finally refluxed for 5 minutes.

On cooling, the product began to crystallise out of solution. An equal volume of methanol was added to complete the precipitation, and the product was filtered off and washed with methanol.

The product was dissolved in warm dichloromethane (300 cm3) and filtered. Addition of methanol (300 cm3) to the cooled solution produced colourless crystals (77.0 g, 70%), m.p. 1260C (lit. 1270C).

EXAM PLE 2 6-Bromohexyltriphenylphosphonium bromide, (6 in Table 1): An excess of 1 6-dibromohexane (310 g, 125 mol) was heated at 1 000C for 1 hour with triphenylphosphine (65.5 g, 0.25 mol), stirring occasionally with a thermometer. The clear solution became cloudy after about 10 minutes. When left overnight to cool, the product crystallised, and the excess 1 ,6-dibromohexane was recovered by filtration (73% recovery). The product was washed with petroleum (b.p. 40-600C) and dried under vacuum (110.5 g, 88%, m.p. 130-20C).

EXAMPLE 3 Phosphonium salts, (1)(5) and (7)(23) (Table 1): The phosphonium salts were prepared by dissolving the respective phosphine and alkyl halide in stoichiometric quantities (usually 1:1) at a concentration of 0.01 mol of each reactant in 1 5-30 cm3 of solvent, and refluxing for the required time. Details are given in Table 1.

The salts prepared in toluene precipitated out of the hot solvent during the reaction, and were filtered off (or the toluene decanted if the product was a glass or viscous oil) and washed with -petroleum (b.p. 4060 C).

The salts prepared in dichloromethane or chloroform were isolated by concentrating the solution and adding ethanol.

In the case of salts prepared in dimethylformamide as solvent, the solutions remained clear throughout the reaction. The symmetrical bisphosphonium salts, (7) and (1 3), crystallised out of the cooled solution as large crystals, but the unsymmetrical products had to be precipitated by the slow addition, with stirring, of dry toluene, giving the product as a viscous oil which in most cases crystallised after a few minutes stirring.

The solid salts generally gave good elemental analyses (Table 1) and further purification was unnecessary.

EXAMPLE 4 1-Ethylphenylphosphinoyl -6-diphenylphosphinoylhexane (5 in Table 2): 1-Ethylphenylphosphonium-6-triphenylphosphoniumhexane dibromide (57.6 g, 0.08 mol) was suspended in 20% aqueous sodium hydroxide (1 50 cm3) and boiled with rapid stirring in an open flask for 1 hour. The solid bisphosphonium salt quickly reacted and formed an oil layer on the surface of the liquid.

After cooling, the almost solidified oil was separated from the aqueous solution, washed twice with a little water, then twice with dry diethyl ether. Residual traces of water were removed by dissolving the product in the minimum volume of boiling toluene and distilling out some of the solvent.

Cooling produced solid particles. An equal volume of dry ether was then added and the flask stoppered and left overnight in a refrigerator.

The crystallised hydroscopic product was filtered off under a stream of nitrogen, washed with dry ether and dried under a vacuum as colourless crystals (26.0 g, 74% m.p. 88-940C). The rather wide melting range was not altered by recrystallisation, and seemed to be a characteristic of the unsymmetrical bisphosphine oxides.

The other phosphine oxides detailed in Table2 were prepared by the above method. Compounds (1) and (2) were produced as solids in the boiling sodium hydroxide solution, the rest as viscous oils which were crystallised as above by dissolving in hot toluene, or (if sparingly soluble in toluene) in a mixture of toluene and ethanol (2:1 v/v), allowing to cool, and treating with ether.

EXAMPLES 1-Ethylphenylphosphino-6-diphenylphosphinohexane, (2 in Table 3): The bisphosphine dioxide prepared as in Example 4 (12.3 g, 0.028 mol) was dissolved in warm dry toluene (40 cm3) and added to a mixture of trichlorosilane (13.2 g, 9.6 cm3, 0.1 mol), triethylamine (9.6 g, 1 3.5 cm3, 0.1 mol) and dry toluene (120 cm3).

After refluxing for2 hours under a nitrogen atmosphere, the flask was cooled in ice and 50% aqueous sodium hydroxide (150 cm3) was slowly added to destroy the excess trichlorosilane and to dissolve most of the solid present.

The contents of the flask were transferred to a separating funnel, and the aqueous layer removed.

The organic layer was washed twice with deoxygenated water and filtered through glass wool. The aqueous layer was extracted with toluene, which was added to the phosphine solution.

Evaporation of the toluene under vacuum left a thick oil which, when mixed with petroleum (b.p.

40--600C), (30 cm3), and left overnight in a refrigerator, solidified into colourless crystals (7.3 g, 64%), m.p. 44-460C.

All reductions of phosphine oxides to phosphines were carried out by the above method. It was found that phosphines procured from pure phosphine oxides did not require further purification.

Although the invention has been described with particular reference to bisphophines, and intermediates in the preparation thereof, containing predominantly aryl groups, it may be equally applicable to bisphosphines and intermediates in the preparation thereof, containing predominantly alkyl groups.

The phosphines described in this application may be used as ligands in coordination complexes with for example platinum group metals in homogeneous catalysis.

Claims (6)

1. A process for the synthesis of a bisphosphine comprising (i) preparation of a bisphosphonium salt, (ii) hydrolysis of the bisphosphonium salt to yield a bisphosphine oxide and (iii) reduction of the bisphosphine oxide to yield a bisphosphine.

2. Bisphosphines having the general formula A(CH2)nB where A and B are the same or different phosphine moieties having the formula R P R'2P or RR'P where R and R' represent an aryl, aralkyl, alkaryl or alkyl group, and n is an integer from 1 to 10 inclusive.

3. Bisphosphonium salts having the general formula [A'(CH2)nB']2+X2- where A' and B' are the same or different phosphine moieties having the formula R3P, R2R'P, B' 3P or RR'2P where R and R' represent an aryl, aralkyl, alkaryl or alkyl group, n is an integer from 1 to 10 inclusive and X is a divalent anion or two monovalent anions which may be the same or different.

4. Bisphosphine oxides having the general formula A"(O)(CH2)n(0)3" where A" and B" are the same or different phosphine moieties having the formula R2P, RR'P or B'2P where R and R' represent an aryl, aralkyl, alkaryl or alkyl group and n is an integer from 1 to 10 inclusive.

5. Mixed compounds comprising phosphine-phosphine oxides phosphonium salt-phosphine oxides or phosphine-phosphonium salts as claimed in any one of claims2 to 4.

6. A compound as claimed in any one of claims2, 3 or 4 or a mixed compound as claimed in claim 5 in which R and/or R' are/is substituted.